Utility of oral glucose tolerance test in predicting type 2 diabetes following gestational diabetes: Towards personalized care.

BACKGROUND: Women with gestational diabetes mellitus (GDM) are at a seven-fold higher risk of developing type 2 diabetes (T2D) within 7-10 years after childbirth, compared with those with normoglycemic pregnancy. Although raised fasting blood glucose (FBG) levels has been said to be the main significant predictor of postpartum progression to T2D, it is difficult to predict who among the women with GDM would develop T2D. Therefore, we conducted a cross-sectional retrospective study to examine the glycemic indices that can predict postnatal T2D in Emirati Arab women with a history of GDM. AIM: To assess how oral glucose tolerance test (OGTT) can identify the distinct GDM pathophysiology and predict possible distinct postnatal T2D subtypes. METHODS: The glycemic status of a cohort of 4603 pregnant Emirati Arab women, who delivered in 2007 at both Latifa Women and Children Hospital and at Dubai Hospital, United Arab Emirates, was assessed retrospectively, using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Of the total, 1231 women were followed up and assessed in 2016. The FBG and/or the 2-h blood glucose (2hrBG) levels after a 75-g glucose load were measured to assess the prevalence of GDM and T2D, according to the IADPSG and American Diabetes Association (ADA) criteria, respectively. The receiver operating characteristic curve for the OGTT was plotted and sensitivity, specificity, and predictive values of FBG and 2hrBG for T2D were determined. RESULTS: Considering both FBG and 2hrBG levels, according to the IADPSG criteria, the prevalence of GDM in pregnant Emirati women in 2007 was 1057/4603 (23%), while the prevalence of pre-pregnancy T2D among them, based on ADA criteria, was 230/4603 (5%). In the subset of women (n = 1231) followed up in 2016, the prevalence of GDM in 2007 was 362/1231 (29.6%), while the prevalence of pre-pregnancy T2D was 36/1231 (2.9%). Of the 362 pregnant women with GDM in 2007, 96/362 (26.5%) developed T2D; 142/362 (39.2%) developed impaired fasting glucose; 29/362 (8.0%) developed impaired glucose tolerance, and the remaining 95/362 (26.2%) had normal glycemia in 2016. The prevalence of T2D, based on ADA criteria, stemmed from the prevalence of 36/1231 (2.9%) in 2007 to 141/1231 (11.5%), in 2016. The positive predictive value (PPV) for FBG suggests that if a woman tested positive for GDM in 2007, the probability of developing T2D in 2016 was approximately 24%. The opposite was observed when 2hrBG was used for diagnosis. The PPV value for 2hrBG suggests that if a woman was positive for GDM in 2007 then the probability of developing T2D in 2016 was only 3%. CONCLUSION: FBG and 2hrBG could predict postpartum T2D, following antenatal GDM. However, each test reflects different pathophysiology and possible T2D subtype and could be matched with a relevant T2D prevention program.

Inhibition of p90 ribosomal S6 kinase attenuates cell migration and proliferation of the human lung adenocarcinoma through phospho-GSK-3ß and osteopontin.

p90 ribosomal S6 kinase (p90RSK) constitutes a family of serine/threonine kinases that have been shown to be involved in cell proliferation of various malignancies via direct or indirect effects on the cell-cycle machinery. We investigated the role of p90RSK in lung adenocarcinomas and whether the inhibition of p90RSK diminishes cancer progression. Moreover, we investigated the involvement of glycogen synthase kinase-3ß (GSK-3ß) and osteopontin (OPN) in the p90RSK-induced lung adenocarcinoma progression. p90RSK, OPN, and GSK-3ß protein expressions were examined in the A549 human lung adenocarcinoma cell line in the presence and absence of BI-D1870 (BID), a p90RSK inhibitor. Gene expression of anti-apoptotic and pro-apoptotic markers namely Bcl2 and Bax, respectively, were studied by reverse transcription polymerase chain reaction. In addition, the A549 lung adenocarcinoma cell line was characterized for cell proliferation using the MTT assay and cell migration using the scratch migration assay. Our study revealed that total RSK1 protein expression is over expressed in the A549 human lung adenocarcinoma cell line, an effect which is significantly reduced upon pretreatment with BID (69.32 ± 12.41 % of control; P < 0.05). The inhibition of p90RSK also showed a significant suppression of cell proliferation (54.3 ± 6.73 % of control; P < 0.01) and cell migration (187.90 ± 16.10 % of control; P < 0.01). Treatment of the A549 cells with BID regressed the expression of Bcl2 mRNA (56.92 ± 6.07 % of control; P < 0.01). BID also regressed protein expression of OPN (79.57 ± 5.32 % of control; P < 0.05) and phospho-GSK-3ß (73.04 ± 8.95 % of control; P < 0.05). The p90RSK has an essential role in promoting tumor growth and proliferation in non-small cell lung cancer (NSCLC). BID may serve as an alternative cancer treatment in NSCLC.

p90 ribosomal S6 kinase: a potential therapeutic target in lung cancer.

A global survey of cancer has shown that lung cancer is the most common cause of the new cancer cases and cancer deaths in men worldwide. The mortality from lung cancer is more than the combined mortality from breast, prostate and colorectal cancers. The two major histological types of lung cancer are non-small cell lung cancer (NSCLC) accounting for about 85 % of cases and small cell lung cancer accounting for 15 % of cases. NSCLC, the more prevalent form of lung cancer, is often diagnosed at an advanced stage and has a very poor prognosis. Many factors have been shown to contribute to the development of lung cancer in humans including tobacco smoking, exposure to environmental carcinogens (asbestos, or radon) and genetic factors. Despite the advances in treatment, lung cancer remains one of the leading causes of cancer death worldwide. Interestingly, the overall 5 year survival from lung cancer has not changed appreciably in the past 25 years. For this reason, novel and more effective treatments and strategies for NSCLC are critically needed. p90 ribosomal S6 kinase (RSK), a serine threonine kinase that lies downstream of the Ras-MAPK (mitogen activated protein kinase) cascade, has been demonstrated to be involved in the regulation of cell proliferation in various malignancies through indirect (e.g., modulation of transcription factors) or direct effects on the cell-cycle machinery. Increased expression of RSK has been demonstrated in various cancers, including lung cancer. This review focuses on the role of RSK in lung cancer and its potential therapeutic application.